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Melanoma: its only skin deep or is it?

Skin cancer is actually quite nicely treatable despite the horror stories you might hear. But, here is the catch….only when it is caught early. Melanoma (the lethal form of skin cancer) before it spreads is fairly easy to treat…scary but treatable. Unfortunately, as is the case with many cancers, once it has spread to different sites of your body, in a process called metastasis, it is very difficult to treat. The most severe stage of the disease is known as stage IV metastatic melanoma, and this is a deadly incurable form of the disease. Sadly, the only approved drug, a type of chemotherapy, only reduced the cancer in 10% of patients. What’s even worse is that even in those 10% where the drug seems to work, the patients will still die of the disease. This drug, like many, poison the cell as it undergoes cell division in a process known as proliferation. To make a long story short, any dividing cell is potentially vulnerable to this drug so it is a very broad killer of cells. The melanoma cells are slightly more sensitive to this drug, but so are hair follicles, cells lining the gut, and other rapidly dividing cells in your body.

As is the case for many forms of cancer, researchers are looking for agents that might be a little bit (or a whole lot) more selective in targeting the cancer cell itself and sparing the normal cells (like the hair follicles, etc.). Melanoma is one cancer that has been probably the most studied in this area. One such area of investigation is the use of ‘immunotherapy’ to try to treat the disease. In these types of therapies certain drugs or proteins are used to help the patients’ own immune system to defend against the cancer. One of these developed drugs is an antibody known as ipilimumab or anti-CTLA4. This antibody binds CTLA4 that is present on the T cell in hopes of increasing the anti-T cell function against the cancer. It does seem to work in some patients who receive this in addition to another agent. This other agent is a protein that is found highly expressed on the cancer cells itself known as gp100. This protein is given as a vaccine to help boost the T cell response against the cancer. These two together do show some promise in some patients who have stage IV melanoma. However, at the moment the final clinical trials are being conducted, so it is not widely available and not proven yet.

Other companies are developing drugs that interfere with signaling pathways that are highly activated in cancer cells and less so in on cancer cells. 50% of all patients with advanced melanoma are known to have mutations in a pathway that leads to activated growth. The mutations map to a protein (enzyme) known as BRAF. This mutation keeps the enzyme protein in the active state that leads to continued growth where in normal cells the protein is keep in an inactive state. Chemical drugs have been found that bind to a certain region in the protein that blocks this mutated protein and thus helps to either kill the cell expressing the mutated protein BRAF or at least stop it from being active. Again, this novel drug is still undergoing testing in clinical trials and if it passes muster it will be released for use in cancer centers.

Limitations: There are certainly going to be some limitation that make these and probably most future therapies less effective that we wish. One has to do with cost. Immunotherapies tend to be very expensive. The antibodies or proteins cost a lot to make and the patient ends up paying tens of thousands of dollars per year (sometimes more). The novel chemical drugs are usually more expensive than existing drugs as the drug company passes off the cost of development to the consumer (the cancer patient). The other issue is that even with these new ‘cancer specific’ drugs, different patients will react differently. It is VERY hard to predict which patients will respond well or not. For the BRAF inhibitor discussed above, it is fairly easy to determine which patients to give the drug to (the 50% of the patients who have the mutation and not that ones that do not have mutated forms of BRAF). But, it is another thing to know which patients will respond and which will not. The same goes for the immunotherapies. No one can predict which patients will response to immunotherapies…we just don’t know enough about the millions of different things that happen in human bodies that can interfere with a good anti-cancer immune response.

So, lest you get too depressed and think that no one is doing anything about it…millions of dollars and some of the world’s brightest scientist and clinicians are working to solve this problem of the lethality of late stage skin cancer. But, it takes time and it is complex.

Thankyou for reading and do let me know if you have any further questions/comments about advanced forms of skin cancer or cancer in general. Be sure to visit my cancer information website at Cancer Made Simple!